The present invention relates to the separation of plasma or serum from a blood sample, and more particularly, to a device for achieving such separation in a highly-automated or automation-ready fashion.
In current practice, plasma or serum is typically separated from blood cells of the blood sample by placing whole liquid or clotted blood, respectively, in a tube, and placing the tube in a swinging-bucket type centrifuge. Upon activation, the centrifuge rotates rapidly, causing the tube to acquire a horizontal position. The cells, being heavier than the plasma or serum, migrate to the end of the tube furthest from the center of rotation, thus producing separation of the various components of the sample. In order to form a barrier between the blood constituents after separation, the tube preferably contains a gel that has a specific gravity in between that of the plasma and that of the cells. During the centrifugation, this gel forms a barrier between plasma and cells to prevent remixing when the spin is complete, and the tubes return to their vertical position.
The above procedure is time-consuming, requiring an extended period of centrifugation to achieve the desired results because of the lengthy migration path of the red blood cells along the tube and the need for the gel barrier to form.
U.S. Pat. No. 3,190,547 to J. J. Shanley discloses a centrifuge wherein bottles are located below evacuated plasma receivers. A plurality of such bottle and receiver pairs is rotated about an axis parallel to the axis of each pair, which axis passes through a bottle and receiver. Consequently, upon rotation of the bottles about this axis, red cells migrate toward the outer walls of the sample bottles. Upon completion of the centrifuging, the sample bottle and plasma receivers are connected through hollow needles situated in self-sealing stoppers in each member of the pair, and the plasma is drawn into the plasma receivers. Subsequently, the plasma receivers are spun at a higher rotational velocity (with the specimen bottles being stationary) to produce further separation of the materials drawn therein.
The mechanism is very complex, requiring two separately-driven rotating shafts, two different hollow needles to affect interconnection of the bottle and the receiver, rectangular shaped or other non-cylindrical specimen bottles to ensure that the bottles do not rotate about their own axes. This procedure further requires proper registration of the needle with the sample bottle. To provide proper alignment with the various strata in the specimen bottle, a readily movable self-sealing stopper in the specimen bottle is employed to assist in the search for the strata of the material desired. This procedure may require opening of the specimen bottle to locate the strata interface, thus compromising the sterility of the specimen and possibly endangering the laboratory staff.
U.S. Pat. No. 6,398,705 to Grumberg, et al., teaches a device for rapid separation of plasma or serum from red blood cells. The device includes a rotating drum for spinning a plurality of pairs of head-to-head tubes held in coaxial fashion by a fixture. Each pair of tubes consists of a primary (sample) tube containing a blood sample, and an empty collection tube, under vacuum. The fixture also holds a hollow needle having two sharp ends in between the head-to-head tubes. The tubes must have self-sealing stoppers or caps so that the blood flows only through the needle and does not spin out of the tubes.
When the drum rotates, the red cells migrate to one side of the primary tube. After the separation is completed, and while the centrifuge is still spinning, the two tubes are forced to slide towards each other so that the needle penetrates both stoppers, allowing plasma or serum to flow from the primary tube to the collection tube. The plasma flows into the collection tube due to the partial vacuum in the collection tube and the pressure developed by the centrifuging action in the primary tube.
It must be emphasized that the art disclosed by U.S. Pat. No. 6,398,705 is a significant improvement in relation to the methods and devices previously known in the art, with respect to degree of automation, safety, and separation time. These advances notwithstanding, there remains a great deal of room for improvement. It would be highly desirable to reduce the time required for loading and unloading the plurality of fixtures. It would be highly desirable to reduce the requisite times and labor for assembly and disassembly of each pair of tubes and needle and fixture arrangement.
In common practice, the stopper of the collection tube must be removed to permit sampling of the separated plasma or serum fraction for analysis. In addition to the time and labor expenditures, there is a finite safety risk in removing the stoppers and exposing laboratory personnel to blood samples. Often, this safety risk is compounded by pressure differentials between the collection tube and the environment, resulting in a potentially hazardous aerosol of serum/plasma.
Finally, in transferring the serum/plasma fraction of a blood sample from the sample tube to the corresponding collection tube, care must be taken to preserve the identification of the blood sample on the collection tube (double labeling, etc.). This adds an additional step to the sample preparation process, and perhaps more significantly, introduces an additional possibility for error in a field in which error tolerance is extremely low.
There is thus a widely recognized need for, and it would be highly advantageous to have a device and method for separating blood products that enables a much higher degree of automation and a higher level of safety with respect to the known devices. It would be of particular advantage to have a device that allows for quick and facile sampling by an automatic sample analyzer. It would be of further advantage if such a device would be simple in construction, inexpensive, and easy to manufacture.